Is DES p.Arg15Pro (c.44G>C) pathogenic?

DES p.Arg15Pro (c.44G>C) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely pathogenic (0.927); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DES p.Arg15Pro (c.44G>C)?

DES p.Arg15Pro (c.44G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is DES p.Arg15Pro (c.44G>C) in the general population?

DES p.Arg15Pro (c.44G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DES p.Arg15Pro (c.44G>C)?

AlphaMissense predicts likely pathogenic (score 0.927) — an in-silico prediction, not a clinical call.

DES p.Arg15Pro

c.44G>C · VCV4011018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.927 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.927	likely pathogenic
REVEL	0.779	moderately pathogenic-leaning
SaProt	LLR -10.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 0.48, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DES
Protein: p.Arg15Pro
Coding: c.44G>C
MANE Select: NM_001927
Type: single nucleotide variant
Location: chr2:219418506 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 15: the 'head' region

Full DES gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DES p.Arg15= Likely benign ★★ same residue
DES p.Arg15Ser Uncertain significance ★★ ⚠ same residue
DES p.Arg15Cys Uncertain significance ★ ⚠ same residue
DES p.Arg15Gly Uncertain significance ★ ⚠ same residue
DES p.Arg212Ter Pathogenic/Likely pathogenic ★★ same condition
DES p.Arg454Trp Pathogenic/Likely pathogenic ★★ same condition
DES p.Glu401Asp Pathogenic/Likely pathogenic ★★ same condition
DES c.1245-3T>G Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/des-p-arg15pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown